Philadelphia, PA, January 8, 2008 – Schizophrenia is a developmental disorder with a large genetic component contributing to increased risk. Available antipsychotic medications treat some of the symptoms of schizophrenia, but are typically effective in only a subset of patients. Unfortunately, it is difficult to predict the effectiveness of a specific drug in any given individual with schizophrenia. John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, notes that “in this era of medicine, the selection of particular antipsychotic medications for particular patients with schizophrenia is more art than science. We have been seeking objective guides, perhaps biological tests, which would inform this process.” A new study published in the January 1st issue of Biological Psychiatry provides some interesting data to aid in that goal.
The authors report that differential effectiveness of antipsychotic treatment was predicted, in a subset of patients with schizophrenia, by variants of the gene encoding for the regulator of G-protein signaling 4 (RGS4), a protein that regulates the functional consequences of activating neurotransmitter receptors. Dr. Daniel Campbell, corresponding author for this article, explains these results: “By applying genetic analysis to the NIMH-funded Clinical Antipsychotic Trials of Intervention Effectiveness, we show that variants in a specific gene, RGS4, predict the effectiveness of different antipsychotic treatments. Our results also indicate that the predictive power of the RGS4 genetic variants differed between patients of self-reported African and European ancestry, and thus emphasize the importance of including multiple ethnic groups in a study.”
The authors importantly note that their results will require replication, but the findings indicate that RGS4 contributes to both the severity of schizophrenia symptoms and the response to antipsychotic treatment. Dr. Krystal adds, “While this type of information is not yet ready to guide clinical practice, since the RGS4 variants explain only a small component of overall patterns of treatment response, these data provide an example of “pharmacogenomics”, the approach that will very likely ultimately guide treatment.”
Notes to Editors:
The article is “Ethnic Stratification of the Association of RGS4 Variants with Antipsychotic Treatment Response in Schizophrenia” by Daniel B. Campbell, Philip J. Ebert, Tara Skelly, T. Scott Stroup, Jeffrey Lieberman, Pat Levitt and Patrick F. Sullivan. Drs. Campbell, Ebert, and Levitt are affiliated with the Department of Pharmacology at Vanderbilt University in Nashville, Tennessee. Dr. Levitt is also with the Vanderbilt Kennedy Center for Research on Human Development at Vanderbilt University. Drs. Skelly and Sullivan are from the Department of Genetics, while Dr. Stroup is from the Department of Psychiatry, at the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Dr. Lieberman is affiliated with the Department of Psychiatry at Columbia University and the New York State Psychiatric Institute in New York, New York. Dr. Sullivan is also with the Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden. The article appears in Biological Psychiatry, Volume 63, Issue 1 (January 1, 2008), published by Elsevier.
Full text of the article mentioned above is available upon request. Contact Jayne M. Dawkins at (215) 239-3674 or ja.dawkins@elsevier.com to obtain a copy or to schedule an interview.
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This international rapid-publication journal is the official journal of the Society of Biological Psychiatry. It covers a broad range of topics in psychiatric neuroscience and therapeutics. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and treatment of major neuropsychiatric disorders. Full-length and Brief Reports of novel results, Commentaries, Case Studies of unusual significance, and Correspondence and Comments judged to be of high impact to the field are published, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Concise Reviews and Editorials that focus on topics of current research and interest are also published rapidly.
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Biological Psychiatry